Cytokinetics is developing tirasemtiv (CK-2017357), a therapy to improve symptoms of muscle weakness and fatigue in people with myasthenia gravis (MG) and other neuromuscular disorders. Results from clinical trials have been positive, but the drug is not yet approved for use in the United States or Europe.

How tirasemtiv works

Muscle contraction begins when a motor nerve sends a signal to muscle cells. The signal triggers the release of calcium from its storage site — called the sarcoplasmic reticulum — into the fluid inside the muscle cell, or sarcoplasm. When calcium attaches to troponin, a protein complex in muscle cells, it brings the muscle proteins actin and myosin together, causing a muscle to contract.

The problem in MG is that autoantibodies — antibodies produced by patient’s own immune system —block the signals from motor nerves to muscles, so muscles receive less stimulation. Tirasemtiv makes the troponin complex in skeletal muscle cells more sensitive to calcium, which enhances the amount of force a muscle can generate in response to the same degree of nerve stimulation. It also keeps the muscle from tiring out as quickly.

Tirasemtiv in clinical trials

Researchers tested tirasemtiv in 32 patients with MG and muscle weakness in a Phase 2a clinical trial (NCT01268280). Patients were randomized to receive either placebo, 250 mg of tirasemtiv, or 500 mg of tirasemtiv, given in a single dose roughly once a week. Researchers tested the effectiveness of tirasemtiv using various scores of muscle strength and endurance in the hours after the dose was given.

Results of this trial, announced by Cytokinetics in March 2013 and published in the journal Neurotherapeutics in 2015, showed that tirasemtiv improved muscle function in a dose-dependent manner, meaning that patients taking higher doses showed more improvement. The drug was well-tolerated and no participant had to stop taking it because of adverse effects.

It has also been tested in several clinical studies involving patients with amyotrophic lateral sclerosis (ALS). All the studies supported its safety and ability to improve muscle function. Tirasemtiv has received orphan drug status in both the United States and Europe as a potential treatment for ALS.

Additional information

Tirasemtiv improves muscle function in MG patients. It does not treat the underlying cause or keep the disease from getting worse.

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